Tryba 1988.

Methods	Randomised controlled trial
Participants	Baseline characteristics Number randomised: 400 participants Number analysed: 400 participants Ranitidine Age (years; median (SD)): 56.8 (16.7) Number of participants (n): 200 Gender (female; %): 72.5 Pirenzepine Age (years; median (SD)): 57.7 (16.8) Number of participants (n): 200 Gender (female; %): 78.5 Inclusion criteria Participants on general surgical ICU unit or anaesthesiological ICU unit Expected duration of stay at ICU > 36 hours Exclusion criteria Surgery of upper gastrointestinal tract History of ulcer disease in the last 12 months Expected long‐term respiratory support Baseline imbalances: no significant differences
Interventions	Ranitidine Dose (total/d): 200 mg Duration of treatment (days, mean (SD)): 3.8 (2.3) Route: IV Intervention: 200 mg ranitidine continuous IV infusion (started within 12 hours after admission to ICU) Concomitant medications: ‐ Pirenzepine Dose (total/d): 50 mg Duration of treatment (days, mean (SD)): 4.1 (3.0) Route: IV Intervention: 50 mg pirenzepine continuous IV infusion (started within 12 hours after admission to ICU) Concomitant medications: ‐ Adherence to regimen: ‐ Duration of trial: October 1984 to November 1986 Duration of follow‐up: unclear, but might be until discharge from ICU
Outcomes	Outcomes sought in review and reported in trial Primary outcomes Gastrointestinal bleeding defined as microscopically detectable bleeding (melena, bloody aspirate, haematemesis) Secondary outcomes Ventilator‐associated pneumonia defined as changes in lungs as seen on X‐ray films and 3 of the following: fever > 38.5°C, leucocytosis, pathogens isolated from a tracheal culture, change in arterial gas balance Gastric pH Adverse events of interventions All‐cause mortality in ICU Duration of intubation: not mentioned. Outcomes sought but not reported in trial All‐cause mortality in hospital Duration of ICU stay (not absolutely clear, but likely 3.8 days ± 2.3 in ranitidin group and 4.1 ± 3.0 in pirenzepine group) Participants requiring blood transfusion Outcomes reported but not used in review Gastric pH values
Notes	Setting: Anaesthesiology Department, Hannover and Bochum, Germany Source of funding: ‐ Conflicts of interest: ‐ Ethics Approval: Study was conducted according to the drug law. No further information Informed Consent: ‐ Clinical Trials Registration: ‐ Sample Size Calculation: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: not clearly mentioned in the study report
Allocation concealment (selection bias)	Unclear risk	Comment: not clearly mentioned in the study report
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: This was not a placebo‐controlled trial, and the different modes of administering study interventions would not have made it possible to blind study personnel and participants. Therefore, high risk of performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear whether outcome assessors were blinded. GI bleeding was an objective outcome that was detected as per the definition in the study protocol
Blinding (detection bias) Nosocomial pneumonia	Low risk	Comment: unclear whether outcome assessors were blinded. Pneumonia was an objective outcome that was detected as per the definition in the study protocol. Outcome assessor was blinded to study aims
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Unclear risk	Comment: Outcome assessor was blinded to study aims. Therefore, low risk of bias
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants were part of the analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes have been reported
Other bias	Low risk	Comment: No additional biases were detected